Stress imaging may be performed directly by a provider trained in stress imaging or by a nurse, exercise physiologist, or medical technician operating under the provider's supervision. Sonographers and nuclear technicians trained in image acquisition and machine operations for the respective modalities are the primary technical personal. A cardiologist trained in echocardiography and/or nuclear imaging provides the interpretations.[4][11]

Patient instructions: No food/drink for 4 to 8 hours before any stress test. No caffeine or phosphodiesterase inhibitors for 48 hours before the nuclear MPI regadenoson stress test. No beta-blockers on the day of dobutamine stress echocardiogram.[8]

Methods of Cardiac Stress Testing [8]

Exercise Tolerance Testing

• Uses a standardized exercise protocol, most commonly the 7-staged Bruce protocol 
• The Bruce protocol involves incremental increases in walking speed and incline on a treadmill every 3 minutes until 85% of the maximal predicted heart rate is achieved (maximal predicted heart rate = 220-patient age)
• EKG telemetry rhythms, hemodynamic changes, and clinical responses to exercise are monitored before, during, and after exercise[8]

Stress Echocardiography (Echo)

• Stress is induced with either exercise or pharmacologically with dobutamine. 
• Up titrate dobutamine from 5 to 10 mcg/kg/min, increasing by 10 mcg/kg/min every 3 min to a total of 40 to 50 mcg/kg/min until 85% of maximum predicted heart rate is achieved (220-age)[2][8]
• Side effects: chest pain, nausea, vomiting, flu-like symptoms, arrhythmias [2] 
• Baseline echo is obtained and used as rest images.
• Exercise stress echo is obtained immediately after achieving the patient’s goal heart rate, ideally within 1 minute.[8]
• Pharmacologic stress echo is obtained during the infusion of dobutamine.

Stress Myocardial Perfusion Imaging (MPI)

• Stress is induced with either exercise or pharmacologically with regadenoson.
• 0.4mg IV push over 10 seconds
• Side effects: bronchospasm, flushing, headache, nausea, chest discomfort[2] 
• Isotope options include thallium-201 (Tl-201), technetium-99 sestamibi (Tc-99m), or technetium-99 tetrofosmin 
• Images are obtained before, during, and after stress (each scan takes about 20minutes).[8] 
• Obese patients may need a 2-day test, with stress and post-stress rest images each accompanied by a low-dose tracer injection.
• Imaging may be obtained by SPECT or PET scan.[1]

Complications can occur during cardiac stress testing, and these include:

1. Cardiopulmonary Arrest
2. Myocardial infarction
3. Hypotension/Hypertension
4. Arrhythmias
5. Bronchospasm
6. Adverse or allergic reactions to isotope/pharmacologic agent[8]

Exercise EKG Stress Test (Exercise Treadmill Test, ETT)

Clinical interpretation provides information on exercise capacity (if not pharmacologic) and stress-induced symptoms, hemodynamic changes, and electrocardiogram abnormalities. Recurrence of angina, hypotension, ventricular arrhythmias, and concerning EKG changes such as horizontal or downsloping ST depression > 1 mm for at least 60-80 ms suggest ischemic coronaries, constituting a positive test. Unlike ST elevations, ST depressions do not localize to specific vessels but still indicate ischemic disease needing further evaluation with image testing or coronary angiography.[8] ETT can also reveal chronotropic incompetence, the failure to increase heart rate appropriately, leading to exertional symptoms such as dizziness, which suggests conduction pathologies.[5] The ability to achieve at least 10 METs on the ETT protends an excellent prognosis, regardless of the extent of coronary disease.[8]

Duke treadmill score (DTS) is a prognostic tool summarizing the results of an ETT.  

DTS = exercise time – (5 × ST deviation) – (4 × exercise angina)

• Exercise angina is defined as follows : 0 = none, 1 = non-limiting, 2 = exercise-limiting
• DTS >= 5 is low-risk, –10 to +4 is moderate risk, and <= -11 high-risk[12] 
• Low-risk= 0.25% 1-year mortality; 40.1% risk of single-vessel 75% stenosis
• Moderate-risk= 1.25% 1-year mortality; 67.3% risk of single-vessel 75% stenosis
• High-risk= 5.25% 1-year mortality; 99.6% risk of single-vessel 75% stenosis[13]

Stress Echocardiography:

A normal stress echocardiography test demonstrates global myocardial normokinesis at rest and then a normokinetic or hyperkinetic response to stress. Regional wall motion dysfunction (hypokinetic, dyskinetic, akinetic) that occurs at rest and stress represents scar tissue, likely from a prior infarct. Dysfunction that occurs only during stress suggests ischemia. Dysfunction present at rest, which improves at minimal stress and then worsens again at peak stress, indicates viable hibernating myocardium. Dysfunction at rest with sustained improvement on various levels of stress predicts stunned myocardium. Negative stress echocardiography test confers a 0.5% to 0.8% 1-year risk of cardiac death or nonfatal myocardial infarct (MI).[1] 

Stress Nuclear (SPECT-MPI and PET-MPI):

As a potent coronary vasodilator acting on the A2A receptor, regadenosin increases significantly more flow to healthy vessels than obstructed vessels. This imbalance of blood blow is detected as a perfusion defect in a diseased vessel territory, ischemic EKG changes, or recurrence of symptoms.[8] 

A normal SPECT stress demonstrates global, uniform isotope uptake at rest and then uniformly increased uptake at stress. Regional reductions in uptake during both stress and rest, termed a fixed defect, suggest scar tissue likely secondary to infarct. A relatively lower increase in tracer uptake in specific vascular territories during stress suggests reduced blood flow from stenosed coronary vessels.[1] The diffuse, multi-vessel ischemic disease may still show uniform uptake but can be detected by an increased left ventricular cavity size during stress.[8] Myocardial viability can be assessed with additional images at 18 to 24 hours post initial scan. Regions that on initial resting images lacked uptake will demonstrate a delayed uptake on re-imaging if the myocardium is viable since functional N-K-ATPase in living myocyte cell membranes will eventually uptake tracer, termed a reversible resting defect. Negative stress SPECT-MPI confers a 0.85% 1-year risk of cardiac death or MI. In a clinically stable patient without new symptoms, a normal SPECT-MPI affords a five year warranty period. Worse perfusion impairments, worse ejection fractions, and worse wall motion correlate with an increased likelihood of an adverse cardiac event.[1] 

Like SPECT, PET offers perfusion information and provides more quantitive measures of such and metabolism. PET can more precisely identify perfusion defect location, severity, and extend, including assessing the distal coronary microcirculation. While PET is more accurate than SPECT with relative immunity to attenuation artifacts, its higher expense and infrequent availability make it less commonly used.[1]

Cautions

False Positives 

Patients with LBBB or RV pacing are best evaluated with vasodilator MPI. In LBBB or RV-paced patients, the septum contracts later than the rest of the LV, requiring less blood flow. This physiologic septal hypoperfusion is exaggerated with exercise and reduced by a vasodilator. Therefore vasodilator MPI is preferred to exercise to avoid false positives.[1] Stress MPI can produce false-positive fixed defect signals from tissue attenuation in the inferior wall distribution due to diaphragmatic elevation (most common in men) or anterior wall distribution due to large breast tissue (most common in women).[8] These attenuation artifacts will be fixed, but unlike scar, they will demonstrate preservation of wall thickening between diastole to systole on gated images.[1] Other pathological conditions such as hypertrophic cardiomyopathy, severe LVH, and dilated or infiltrative cardiomyopathies may exhibit perfusion abnormalities on MPI not attributable to CAD.[1] False-positive and false-negative results are common among women ETT.[1][8] 

False Negatives

False-negative results are common in older women with small LV cavities since LVH, and their hyperdynamic left ventricular function impairs the sensitivity of both stress echo and stress NPI to detect abnormalities.[1] False-negative MPI can occur in a triple vessel or left main disease if only relative perfusion is assessed since a balanced perfusion reduction may be misread as normal.[1] 

Management of Positive Test

All positive stress tests warrant a discussion with the patient regarding further revaluation. A positive exercise treadmill test is followed with either stress imaging or high enough concern for patients interested in possible therapeutic interventions directly to coronary angiography. Similarly, a positive stress imaging test indicates a consideration for coronary catheterization.[8] The ACC/AHA apply post-test results to prognostic classifications based on given stress image test findings. The post-test classifications describe mortality risk, include low (<1%), intermediate (1 to 3%), and high (>3%) 1-year mortality risk. ACC/AHH recommends coronary angiography be performed in high-risk post-test patients, observation/medical management in low-risk post-test patients, and further evaluation and individualized clinical judgment in intermediate-risk post-test patients.[2] Providers must caution over-reliance on stress image findings, as each patient's clinical characteristics, including symptoms, CAD risk factors, and exercise capacity, also significantly impact risk profiles and management choices.[2] Angiography can definitively diagnose CAD and offer therapeutic interventions such as percutaneous coronary intervention or coronary artery bypass graft revascularization.[8]

Provider risk stratifies patients presenting with signs and symptoms of new or progressive CAD to deliver early, appropriate preventative and interventional patient care. Initial history and physical exam can gather data on risk factors and clinical signs of coronary disease. All health professional team members, including nurses, nurse practitioners, primary care providers, provider assistants, and cardiologists, must be aware of early clinical signs and CAD symptoms to help facilitate early evaluation. A high index of CAD suspicion in at-risk populations and early investigation helps reduce adverse cardiac events and improve quality of life.[8]

No large, randomized trial compares all stress imaging modalities to identify a superior choice. A meta-analysis found that negative echocardiography and MPI stress tests accurately identified patients with a low yearly risk of myocardial infarction or cardiac death. Guidelines proposed by major national societies, such as the American College of Cardiology and American Heart Association (ACC/AHA), American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology, American Society of Echocardiography, all help providers apply the best diagnostic testing, including stress imaging, to provide optimum evidence-based patient care.[3][4][7][6] 

Recommendations on image selection focus on specific patient factors (specified in previous sections) and on the local facility's factors, including the training of those interpreting tests, the experience and skills of the sonographers or nuclear technicians, and the center's overall volume of tests. This highlights each member of the health care team's importance in delivering effective stress testing, as each member must be up-to-date, competent, and complementary to the team. A collaborative approach among various health care providers and shared-decision making with the patient allows for optimal medical care.[2]

Nurses/Medical Assistants

1. Verify correct patient information in the electronic medical record and completion of the patient consent form. 
2. Verify the correct placement of 12-lead EKG, blood pressure cuff, and pulse oximetry for monitoring. 
3. Establish IV access for nuclear medication delivery/pharmacologic stress medication delivery.
4. Monitor the patient during the procedure.

Echosonographers/Nuclear Imaging Technicians

1. Operate imaging equipment and perform image acquisition with either an ultrasound machine or nuclear scanner (SPECT or PET) 
2. Monitor the patient during the procedure.[11]

Monitor vital signs, EKG changes, and patient symptoms during, before, and after the stress test.

Terminate the test and alert a provider if any concerning findings develop such as:

1. ST elevations >1 mm in leads without Q waves (other than V1 or AVR)
2. Moderate to severe angina
3. Near syncope
4. Cyanosis or decreasing oxygen saturation
5. Sustained ventricular tachycardia
6. Drop-in systolic blood pressure >10 mmHg from baseline
7. Patient desires to stop [4]